Evaluation of Polymorphisms, Mutations, and Protein Expression by Automated Quantitative Immunohistochemistry (AQUA) in the LapatinibTargets and Metabolic Pathway in Samples From E5803

OBJECTIVES:

• To determine the association between polymorphisms in drug metabolizing enzymes and lapatinib ditosylate-associated toxicity in patients with hormone-sensitive recurrent prostate cancer receiving lapatinib ditosylate on clinical trial ECOG-E5803.
• To determine the association between mutations in EGFR, HER-2 and Kras; protein expression of HER2, EGFR, MAPK and AKT; polymorphism controlling androgen synthesis; and progression-free survival.

OUTLINE: Tissue and blood samples collected from patients enrolled on clinical trial ECOG-E5803 are analyzed for correlative studies. Samples are assessed for HER2, EGFR, MAPK, and Akt; EGFR mutations and polymorphisms in CYP3A4; Ras mutations; recently identified mutations in HER2-neu and Kras; and additional polymorphisms in the lapatinib ditosylate metabolic pathway by automated quantitative IHC. Predictors of efficacy and toxicity are analyzed, including markers in the EGFR pathway as predictors of progression-free survival.